BACKGROUND: Identification of screening tests for the detection of head and neck cancer (HNC) at an early stage is an important strategy to improving prognosis. Our objective was to identify plasma circulating miRNAs for the diagnosis of HNC (oral and laryngeal subsites), within a multicenter International Head and Neck Cancer Epidemiology consortium. METHODS: A high-throughput screening phase with 754 miRNAs was performed in plasma samples of 88 cases and 88 controls, followed by a validation phase of the differentially expressed miRNAs, identified in the screening, in samples of 396 cases and 396 controls. Comparison of the fold changes (FC) was carried out using the Wilcoxon rank-sum test and the Dunn multiple comparison test. RESULTS: We identified miR-151-3p (FC = 1.73, P = 0.007) as differentially expressed miRNAs in the screening and validation phase. The miR-151-3p was the only overexpressed miRNA in validation sample of patients with HNC with early stage at diagnosis (FC = 1.81, P = 0.008) and it was confirmed upregulated both in smoker early-stage cases (FC = 3.52, P = 0.024) and in nonsmoker early-stage cases (FC = 1.60, P = 0.025) compared with controls. CONCLUSIONS: We identified miR-151-3p as an early marker of HNC. This miRNA was the only upregulated in patients at early stages of the disease, independently of the smoking status. IMPACT: The prognosis for HNC is still poor. The discovery of a new diagnostic biomarker could lead to an earlier tumor discovery and therefore to an improvement in patient prognosis.

Cancer Epidemiology Research Programme IDIBELL Catalan Institute of Oncology L'Hospitalet de Llobregat Spain

Cancer Epidemiology Unit Centro di Riferimento Oncologico Aviano IRCCS Aviano Italia

Cancer Epidemiology Unit Department of Medical Sciences Università di Torino Torino Italia

Cancer Registry of Norway Oslo Norway

Consortium for Biomedical Research in Epidemiology and Public Health Madrid Spain

Department of Cardiac Thoracic Vascular Sciences and Public Health Università di Padova Padova Italia

Department of Hygiene Epidemiology and Medical Statistics School of Medicine National and Kapodistrian University of Athens Athens Greece

Department of Life Sciences and Public Health Section of Genomic Medicine Università Cattolica del Sacro Cuore Roma Italia

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Department of Woman and Child Health and Public Health Public Health Area Fondazione Policlinico Universitario A Gemelli IRCCS Roma Italia

Dipartimento Patologia Testa Collo e Organi di Senso Facoltà Medicina e Chirurgia Università Cattolica Sacro Cuore Roma Italia

Dipartimento Scienze dell'Invecchiamento Neurologiche Ortopediche e della Testa Collo Fondazione Policlinico Universitario A Gemelli IRCCS Roma Italia

Division of Cancer Epidemiology and Prevention Aichi Cancer Center Nagoya Japan

Division of Cancer Epidemiology Nagoya University Graduate School of Medicine Nagoya Japan

Institute of Hygiene and Epidemiology 1st Faculty of Medicine Charles University Prague Czech Republic

International Agency for Research on Cancer World Health Organization Lyon France

Leibniz Institute for Prevention Research and Epidemiology BIPS and University of Bremen Faculty of Mathematics and Computer Science Institute of Statistics Bremen Germany

Section of Hygiene University Department of Life Sciences and Public Health Università Cattolica del Sacro Cuore Roma Italia

Stony Brook Cancer Center Stony Brook University Stony Brook New York

Trinity College Dublin School of Dental Science Dublin Ireland

Unit of Medical Genetics Department of Laboratory Science and Infectious Diseases Fondazione Policlinico Universitario A Gemelli IRCCS Roma Italia

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